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A potential role for somatostatin signaling in regulating retinal neurogenesis
Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155210/ https://www.ncbi.nlm.nih.gov/pubmed/34040115 http://dx.doi.org/10.1038/s41598-021-90554-3 |
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author | Weir, Kurt Kim, Dong Won Blackshaw, Seth |
author_facet | Weir, Kurt Kim, Dong Won Blackshaw, Seth |
author_sort | Weir, Kurt |
collection | PubMed |
description | Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a modest, dose-dependent inhibition of photoreceptor generation, while correspondingly increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants but abolished in Sstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed in Sstr2-deficient retinas in vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that, while Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, it is dispensable for normal retinal development. |
format | Online Article Text |
id | pubmed-8155210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81552102021-05-28 A potential role for somatostatin signaling in regulating retinal neurogenesis Weir, Kurt Kim, Dong Won Blackshaw, Seth Sci Rep Article Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a modest, dose-dependent inhibition of photoreceptor generation, while correspondingly increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants but abolished in Sstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed in Sstr2-deficient retinas in vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that, while Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, it is dispensable for normal retinal development. Nature Publishing Group UK 2021-05-26 /pmc/articles/PMC8155210/ /pubmed/34040115 http://dx.doi.org/10.1038/s41598-021-90554-3 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Weir, Kurt Kim, Dong Won Blackshaw, Seth A potential role for somatostatin signaling in regulating retinal neurogenesis |
title | A potential role for somatostatin signaling in regulating retinal neurogenesis |
title_full | A potential role for somatostatin signaling in regulating retinal neurogenesis |
title_fullStr | A potential role for somatostatin signaling in regulating retinal neurogenesis |
title_full_unstemmed | A potential role for somatostatin signaling in regulating retinal neurogenesis |
title_short | A potential role for somatostatin signaling in regulating retinal neurogenesis |
title_sort | potential role for somatostatin signaling in regulating retinal neurogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155210/ https://www.ncbi.nlm.nih.gov/pubmed/34040115 http://dx.doi.org/10.1038/s41598-021-90554-3 |
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